Experiments were performed to determine (1) whether intravenously administered aminophylline inhibits the coronary vasodilating effects of intravenous or intracoronary administration of dipyridamole or adenosine and (2) whether aminophylline locally administered in the coronary artery inhibits the vasodilating action of adenosine given intravenously or injected into the coronary artery. Coronary vasodilator responses to dipyridamole or adenosine were determined before and after administration of aminophylline. Intravenous aminophylline was found to inhibit coronary vasodilatation induced by intravenous or intracoronary dipyridamole or adenosine. After intravenous aminophylline, adenosine administered intravenously or into the coronary artery was 2.5 to 4 times less effective in inducing coronary vasodilatation. Aminophylline injected locally into the coronary artery was also effective in inhibiting coronary vasodilatation induced by intravenous and intracoronary adenosine. The mechanism of this inhibitory phenomenon has not been elucidated. ADDITIONAL KEY WORDSthermodilution flowmeter nitroglycerin acetylcholine coronary sinus blood flow• During our studies to evaluate the coronary vasodilating effects of various agents, we observed that normally effective intravenous doses of dipyridamole, 1 a coronary vasodilator, were not effective in increasing coronary sinus blood flow in dogs previously given aminophylline. In the present paper we report the results of experiments performed to demonstrate inhibition of the coronary vasodilating action of dipyridamole or adenosine by aminophylline. Previous studies had shown that dipyridamole enhances coronary vasodilatation induced by intravenously administered adenosine (1, 2). It was further found that dipyridamole decreases the permeability of the red blood cell membrane to adenosine (3, 4), thus preventing entry of adenosine into the red blood cell where it would be inactivated by the intracellular adenosine deaminase. On the basis of these findings, dipyridamole-induced vasodilatation could be related to an adenosine action. It was for this reason that the present studies were extended to adenosine also.The role of catecholamines, if any, in the inhibition of adenosine-induced coronary vasodilatation by aminophylline was also investigated after beta-receptor blockade. MethodsTwenty-six healthy mongrel dogs were used; all were anesthetized with morphine sulfate, 3 mg/kg subcutaneously, followed in 1 hour by intravenous administration of allobarbital, 12.5 mg/kg, urethane, 50 mg/kg; monoethylurea, 50 mg/kg; and sodium pentobarbital, 8 mg/kg. Femoral arterial blood pressure was recorded on a direct-writing Sanborn Polyviso, from a Statham strain gauge connected to a percutaneously inserted Cournand needle. Coronary sinus blood flow was measured by a thermodilution catheter flowmeter (5) inserted through the jugular vein

SUMMARY1. Recent experimental data support the view that prostaglandins might be involved in autoregulation of coronary blood flow. Since indomethacin blocks prostaglandin synthesis, the present study was performed to determine whether indomethacin also inhibits coronary vasodilatation induced by hypoxia.2. Coronary and systemic haemodynamic and metabolic effects of hypoxia (5 % and 8 % oxygen in nitrogen) were studied in intact, anaesthetized and vagotomized dogs before and after indomethacin. 3. 30 and 60 min after administration of indomethacin coronary blood flow increases produced by hypoxia were considerably lower than those before indomethacin.4. These results are held to lend support to the hypothesis that prostaglandins are involved in the autoregulation of coronary blood flow.

SUMMARY1. In previous studies adenosine has been postulated to be the mediator in coronary blood flow regulation and aminophylline was found to inhibit the coronary vasodilator action of adenosine. The present study was performed to determine whether aminophylline inhibits coronary vasodilatation induced by hypoxia.2. Coronary and systemic haemodynamic and metabolic effects of hypoxia were studied in anaesthetized dogs before and after aminophylline. Aminophylline did not influence coronary vasodilatation induced by hypoxia.3. These results are held not to lend support to the hypothesis that adenosine is the metabolite responsible for the regulation of coronary blood flow.

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Ten intact anaesthetized dogs breathing room air spontaneously (Group A) were compared with ten artificially ventilated dogs (Group B). All were given a bolus of ketamine 2 mg/kg followed by a 20-min infusion of ketamine 0.1 mg/kg/min. In Group A, coronary sinus blood flow, measured with a thermodilution flowmeter, increased by 90% while coronary vascular resistance decreased by 28% and coronary sinus oxygen content decreased by 27%. Heart rate increased by 47%, and arterial pressure by 9%. Cardiac output, calculated by the dye dilution method, increased by 29%, while the left ventricular work index decreased by 50%. Minute ventilation rate decreased by 55%. The Group B dogs were studied as described above, except that they were artificially ventilated. The haemodynamic ahanges were less in Group B, possibly because of improved arterial oxygenation. Heart rate increased by 24%, cardiac output by 21% and arterial pressure by 2%. The coronary sinus blood flow increased by 12% while coronary vascular resistance decreased by 11%. Coronary sinus oxygen concentration decreased by 15%. Five unanaesthetized dogs with electromagnetic flowmeter probes chronically implanted on the aorta and circumflex coronary artery, and an indwelling arterial catheter were studied before, during and after the intravenous administration of ketamine 2, 4, and 8 mg/kg. A dose of 8 mg/kg produced increases in cardiac output, heart rate and arterial pressure of 21%, 44% and 24%, respectively, while coronary blood flow increased 47%. We conclude that, in healthy dogs, ketamine produces an increase in heart rate and cardiac work. A significant increase in coronary blood flow appears to be insufficient to meet the metabolic demands of the myocardium, as the coronary sinus oxygen content decreased.